Abstract

Background

Despite years of effort, a licensed malaria vaccine is not yet available. One of the
obstacles facing the development of a malaria vaccine is the extensive heterogeneity
of many of the current malaria vaccine antigens. To counteract this antigenic diversity,
an effective malaria vaccine may need to elicit an immune response against multiple
malaria antigens, thereby limiting the negative impact of variability in any one antigen.
Since most of the malaria vaccine antigens that have been evaluated in people have
not elicited a protective immune response, there is a need to identify additional
protective antigens. In this study, the efficacy of three pre-erythrocytic stage malaria
antigens was evaluated in a Plasmodium yoelii/mouse protection model.

Methods

Mice were immunized with plasmid DNA and vaccinia virus vectors that expressed one,
two or all three P. yoelii vaccine antigens. The immunized mice were challenged with 300 P. yoelii sporozoites and evaluated for subsequent infection.

Results

Vaccines that expressed any one of the three antigens did not protect a high percentage
of mice against a P. yoelii challenge. However, vaccines that expressed all three antigens protected a higher
percentage of mice than a vaccine that expressed PyCSP, the most efficacious malaria
vaccine antigen. Dissection of the multi-antigen vaccine indicated that protection
was primarily associated with two of the three P. yoelii antigens. The protection elicited by a vaccine expressing these two antigens exceeded
the sum of the protection elicited by the single antigen vaccines, suggesting a potential
synergistic interaction.

Conclusions

This work identifies two promising malaria vaccine antigen candidates and suggests
that a multi-antigen vaccine may be more efficacious than a single antigen vaccine.